Pinch analysis has been supplemented by the Extended Great Composite Curve which was used for chemical reactor, boiler and turbine process design, especially in the combined heat and power applications. Optimal structure of reaction systems for achieving optimal degree of conversion for complex reactions has been developed, taking into account the thermodynamics and kinetics of reactions. A rapid method for finding optimal column sequences of distillation trains has been invented. Combined thermodynamic - mathematical programming design strategy for complex chemical processes has been developed. First, thermodynamic analysis is used to identify possible savings of energy, investments and raw materials. Then, the most promising ideas are used to formulate the process superstructure and discard those widening the search space only. Finally, the simultaneous optimal solution of the system is found using an objective function and mixed integer nonlinear programming. In the field of artificial intelligence the work on expert systems has been upgraded by the use of neural networks to select the optimal thermodynamic method for proposing suitable phase equilibrium method to be used in efficient chemical process design. The proper choice of the thermodynamic method is crucial for the design of distillation columns and evaporators. The developed method can be used for solving other problems of process design and operation. The second part of the reseach was oriented toward the development of an integrated methodology for the synthesis of complex industrial process schemes based on the simultaneous parameter (temperatures, flows, pressures, ...) and topology (unit alternatives, conectivity) optimization, including consideration of sustainability principles. In order to upgrade the capability of the current mixed-integer nonlinear programming (MINLP) optimization techniques, different strategies have been developed: i) prescreening of process alternatives by thermodynamical insights, ii) a Reduced Integer Space (RIS) has been developed for solving large combinatorial heat exhanger networks comprising different types of exchangers, iii) a combined synthesis/analysis strategy for the MINLP synthesis of reactor/separator networks with complex models and iv) a sequential two-stage strategy for the stochastic synthesis of chemical processes in which flexibility and static operability (the ability to adjust manipulated variables) are taken into account. The research group cooperated in several international research projects: PURE (5. EU Framework Programme), Pure Products and Processes Pilot Programme (NATO-CCMS) and several bilateral research projects. Collaboration in international scientific associations (Working Party on Computer Aided Process Engineering, WP CAPE, Core Group of Preventive Environmental Protection Approaches in Europe, PREPARE), in scientific committees of European and World meetings of scientists (ESCAPE, PSE, FOCAPO), in editing boards of scientific journals (Chemical Engineering Research and Design; Chemical and Biochemical Engineering Quarterly; Resources, Conservation and Recycling), in EU Integrated Projects applications and Expressions of Interest.